combination chemotherapy in treating patients with chronic lymphocytic leukemia or lymphocytic lymphoma

Conditions: Leukemia; Lymphoma

Summary: rationale: drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. combining more than one drug may kill more cancer cells. purpose: phase i/ii trial to study the effectiveness of combining ucn-01 with fludarabine in treating patients who have relapsed or refractory chronic lymphocytic leukemia or lymphocytic lymphoma.

objectives: * determine the overall response rate in patients with relapsed or refractory chronic lymphocytic leukemia (cll) or small lymphocytic lymphoma treated with ucn-01 and fludarabine. * assess the molecular changes in cll cells in peripheral blood in patients treated with this regimen. * determine the progression-free and overall survival of patients treated with this regimen. * determine the toxicity of this regimen in these patients. outline: this is a multicenter, dose-escalation study of ucn-01. patients receive ucn-01 iv over 3 hours on day 1 and fludarabine iv over 30-60 minutes on days 1-5. treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of ucn-01 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. once the mtd is determined, 18-46 additional patients receive ucn-01 and fludarabine as above at the recommended phase ii dose. projected accrual: a total of 12 patients will be accrued for the phase i portion of this study within 6 months. a total of 18-46 patients will be accrued for the phase ii portion of this study within 9-23 months.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed chronic lymphocytic leukemia (cll) or b-cell small lymphocytic lymphoma (sll) * cll is defined as: * persistent lymphocytosis greater than 5,000/mm\^3 * cd19/cd5/cd23 positive * kappa or lambda light chain restriction * refractory to or disease progression after 1 or 2 prior treatment regimens * retreatment with oral chlorambucil is allowed and considered a second regimen * at least one of the chlorambucil treatments must be for 3 months or longer * at least 4 courses of cyclophosphamide, vincristine, and prednisone with or without doxorubicin allowed * patients may have received prior fludarabine as first- or second-line therapy if there is evidence of at least partial response and time to progression after initial fludarabine therapy was at least 12 months * no cns involvement by lymphoma patient characteristics: age * 18 and over performance status * ecog 0-2 or * karnofsky 60-100% life expectancy * more than 3 months hematopoietic * see disease characteristics * absolute neutrophil count at least 1,000/mm\^3 * platelet count at least 100,000/mm\^3 * no autoimmune hemolytic anemia or thrombocytopenia secondary to cll or sll requiring ongoing therapy with prednisone or other immunosuppressive agents hepatic * bilirubin normal * ast and alt no greater than 2.5 times upper limit of normal renal * creatinine normal or * creatinine clearance at least 60 ml/min cardiovascular * no symptomatic congestive heart failure * no unstable angina pectoris * no cardiac arrhythmia pulmonary * dlco greater than 60% predicted * fev_1 greater than 70% predicted * no significant underlying pulmonary disease other * no other malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix * no insulin-dependent diabetes mellitus * no other uncontrolled concurrent illness * no ongoing or active infection * no pre-existing peripheral neuropathy grade 2 or greater * no psychiatric illness or social situation that would preclude study compliance * no prior allergic reactions to compounds of similar chemical or biological composition to ucn-01 or other agents in this study * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception prior concurrent therapy: biologic therapy * not specified chemotherapy * see disease characteristics * at least 4 weeks since prior chemotherapy and recovered endocrine therapy * see hematopoietic radiotherapy * no prior mediastinal radiation * at least 4 weeks since prior radiotherapy and recovered surgery * not specified other * no other concurrent investigational agents * no concurrent combination antiretroviral therapy for hiv-positive patients

Keywords: refractory chronic lymphocytic leukemia recurrent small lymphocytic lymphoma